Dynamic regulatory module networks for inference of cell type-specific transcriptional networks.

Dynamic regulatory module networks for inference of cell type-specific transcriptional networks.
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用于推断细胞类型特异性转录网络的动态调控模块网络。

DOI:
10.1101/gr.276542.121
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发表时间:
2022-07
期刊:
影响因子:
7
通讯作者:
Roy, Sushmita
Roy, Sushmita
中科院分区:
生物学1区
文献类型:
--
作者:
Siahpirani, Alireza Fotuhi;Knaack, Sara;Chasman, Deborah;Seirup, Morten;Sridharan, Rupa;Stewart, Ron;Thomson, James;Roy, Sushmita

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转录调控网络的变化可以显著改变细胞命运。为了深入了解转录动力学,一些研究已经在发育过程的不同阶段用平行的转录组学和表观基因组学测量对批量多组学数据集进行了分析。然而,整合这些数据来推断细胞类型特异性调控网络是一个重大挑战。我们提出了动态调控模块网络(DRMNs),一种新的方法来推断细胞类型特异性顺式调控网络及其动态。DRMN整合表达,染色质状态和可访问性来预测上下文特异性表达的顺式调节因子,其中上下文可以是细胞类型,发育阶段或时间点,并使用多任务学习来捕获线性和分层相关上下文的网络动态。我们应用DRMNs来研究三个发育过程中的调控网络动态,每个过程显示出不同的时间关系,并测量调控基因组数据集的不同组合:细胞重编程,肝去分化和正向分化。DRMN确定了驱动细胞类型特异性表达模式的已知和新的调节因子,显示出其广泛的适用性,以检查来自线性和分层相关的多组学数据集的基因调控网络的动态。
Changes in transcriptional regulatory networks can significantly alter cell fate. To gain insight into transcriptional dynamics, several studies have profiled bulk multi-omic data sets with parallel transcriptomic and epigenomic measurements at different stages of a developmental process. However, integrating these data to infer cell type–specific regulatory networks is a major challenge. We present dynamic regulatory module networks (DRMNs), a novel approach to infer cell type–specific cis-regulatory networks and their dynamics. DRMN integrates expression, chromatin state, and accessibility to predict cis-regulators of context-specific expression, where context can be cell type, developmental stage, or time point, and uses multitask learning to capture network dynamics across linearly and hierarchically related contexts. We applied DRMNs to study regulatory network dynamics in three developmental processes, each showing different temporal relationships and measuring a different combination of regulatory genomic data sets: cellular reprogramming, liver dedifferentiation, and forward differentiation. DRMN identified known and novel regulators driving cell type–specific expression patterns, showing its broad applicability to examine dynamics of gene regulatory networks from linearly and hierarchically related multi-omic data sets.
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